This invention relates to new penicillin antibiotics. In particular, this invention relates to 6-acylamido-6-methoxypenicillanic acids and to intermediates useful in the preparation thereof.
Since the discovery of penicillin numerous semisynthetic penicillins have been prepared by the acylation of the penicillin nucleus, 6-aminopenicillanic acid. Thus far the structural modification of the basic penicillin molecule has involved almost exclusively variations of the 6-acylamido side chain.
The preparation of a methoxy substituted penicilloic acid by the reaction of benzyl penicillin with mercuric acetate in methanol has been reported by O. Wintersteiner and H. E. Stavely, (H. T. Clarke, J. R. Johnson, and R. Robinson, eds., The Chemistry of Penicillin, Princeton University Press, Princeton, N.J. 1949, at page 222). F. H. Carpenter et al. have reported a two-step reaction sequence for the preparation of synthetic penicillins, J. Biol. Chem., 176, 915 (1948). In the first step of the sequence, a substituted oxazolone is reacted with an .alpha.-amino-.beta.-mercapto acid to provide a penicillenic acid. The penicillenic acid is then heated in pyridine in the presence of pyridine hydrochloride to provide, in low yield, a synthetic penicillin. However, substituted penicillins other than 6-acylamido-substituted penicillins are not disclosed.
It is an object of this invention to provide 6-methoxypenicillanic acids and certain oxazolone-thiazolidines as intermediates useful in the preparation thereof.